We
report cross-interface emulsification (XiE), a simple method
for the generation of monodisperse droplets of controllable volumes
from picoliter to nanoliter. A device is set up in which a fused-silica
capillary is vibrating across the surface of the continuous phase
(mineral oil) in a reservoir, and the flow of the dispersed phase
(aqueous solution) in the capillary is segmented into monodisperse
droplets at the air/oil interface. We find that the volume of droplets
is mainly dominated by the flow rate and vibrating frequency and not
significantly influenced by other factors, such as the viscosity of
the continuous phase and dispersed phase, the inner diameter of the
capillary (20–100 μm), or the shape of the tip (tapered
or flat). These features reflect high robustness, flexibility, and
precision of XiE for on-demand volume control of droplets. The droplets
automatically assemble into planar monolayer droplet arrays (PMDA)
in flat-bottomed microwells of 96-well plates, offering excellent
convenience for imaging of droplets. As a representative application,
we carry out digital loop-mediated isothermal amplification using
PMDAs with multivolume droplets for the absolute quantification of
nucleic acids. Our results demonstrate that XiE is simple and controllable
for the production of monodisperse size-tunable droplets, and it offers
opportunities for common laboratories, even without microfabrication
facilities, to perform digital quantification, single cell analysis,
and other biochemical assays with high throughput